Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative

Anna Zettergren; Jodie Lord; Nicholas J Ashton; Andrea L Benedet; Thomas K Karikari; Juan Lantero Rodriguez; Alzheimer’s Disease Neuroimaging Initiative*; Anniina Snellman; Marc Suárez-Calvet; Petroula Proitsi; Henrik Zetterberg; Kaj Blennow

doi:10.1186/s13195-020-00754-8

Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative

Alzheimers Res Ther. 2021 Jan 8;13(1):17. doi: 10.1186/s13195-020-00754-8.

Authors

Anna Zettergren¹, Jodie Lord², Nicholas J Ashton^{3

4

5

6}, Andrea L Benedet⁷, Thomas K Karikari³, Juan Lantero Rodriguez³; Alzheimer’s Disease Neuroimaging Initiative*; Anniina Snellman^{3

8}, Marc Suárez-Calvet^{9

10

11

12}, Petroula Proitsi², Henrik Zetterberg^{3

13

14

15}, Kaj Blennow^{3

13}

Affiliations

¹ Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Gothenburg, Sweden. anna.zettergren@neuro.gu.se.
² Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁵ Department of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
⁶ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁷ Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
⁸ Turku PET Centre, University of Turku, Turku, Finland.
⁹ Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
¹⁰ IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
¹¹ Servei de Neurologia, Hospital del Mar, Barcelona, Spain.
¹² Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain.
¹³ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁴ Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
¹⁵ UK Dementia Research Institute at UCL, London, UK.

Abstract

Background: Recent studies suggest that plasma phosphorylated tau181 (p-tau181) is a highly specific biomarker for Alzheimer's disease (AD)-related tau pathology. It has great potential for the diagnostic and prognostic evaluation of AD, since it identifies AD with the same accuracy as tau PET and CSF p-tau181 and predicts the development of AD dementia in cognitively unimpaired (CU) individuals and in those with mild cognitive impairment (MCI). Plasma p-tau181 may also be used as a biomarker in studies exploring disease pathogenesis, such as genetic or environmental risk factors for AD-type tau pathology. The aim of the present study was to investigate the relation between polygenic risk scores (PRSs) for AD and plasma p-tau181.

Methods: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to examine the relation between AD PRSs, constructed based on findings in recent genome-wide association studies, and plasma p-tau181, using linear regression models. Analyses were performed in the total sample (n = 818), after stratification on diagnostic status (CU (n = 236), MCI (n = 434), AD dementia (n = 148)), and after stratification on Aβ pathology status (Aβ positives (n = 322), Aβ negatives (n = 409)).

Results: Associations between plasma p-tau181 and APOE PRSs (p = 3e^-18-7e^-15) and non-APOE PRSs (p = 3e^-4-0.03) were seen in the total sample. The APOE PRSs were associated with plasma p-tau181 in all diagnostic groups (CU, MCI, and AD dementia), while the non-APOE PRSs were associated only in the MCI group. The APOE PRSs showed similar results in amyloid-β (Aβ)-positive and negative individuals (p = 5e^-5-1e^-3), while the non-APOE PRSs were associated with plasma p-tau181 in Aβ positives only (p = 0.02).

Conclusions: Polygenic risk for AD including APOE was found to associate with plasma p-tau181 independent of diagnostic and Aβ pathology status, while polygenic risk for AD beyond APOE was associated with plasma p-tau181 only in MCI and Aβ-positive individuals. These results extend the knowledge about the relation between genetic risk for AD and p-tau181, and further support the usefulness of plasma p-tau181 as a biomarker of AD.

Keywords: Alzheimer’s disease; Plasma phosphorylated tau 181; Polygenic risk score.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / genetics
Amyloid beta-Peptides
Biomarkers
Genome-Wide Association Study
Humans
Neuroimaging
Risk Factors
tau Proteins

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding